Nutritional composition with health promoting action containing oligosaccharides

ABSTRACT

A nutritional composition having beneficial effect in the gastrointestinal tract, especially an anti-adhesion effect on pathogenic micro-organisms and a bifidogenic effect, contains non-digestible oligosaccharides, said oligosaccharides comprising, per daily dosage, 0.3-10 g of oligosaccharides containing at least one terminal arabinose unit. The nutritional composition may furthermore comprise 0.5-10 g of other non-digestible oligosaccharides selected from fructo-oligosaccharides, galacto-oligosaccharides, xylo-oligosaccharides and manno-oligosaccharides. The arabino-oligosaccharides can be obtained conveniently by controlled hydrolysis of arabinose-containing polysaccharides from natural (vegetable) origin.

The present invention relates to nutritional compositions withhealth-promoting action, in particular having a bifidogenic effect andhaving an anti-adhesive effect on pathogenic micro-organisms to theintestinal wall.

More specifically, in a first aspect, the invention relates to such anutritional composition containing at least one oligosaccharide havingat least one terminal arabinose unit.

As used herein, an oligosaccharide means a saccharide consisting of atleast two, up to 20 glycosidically linked monosaccharide units, i.e.having a degree of polymerisation (DP) of 2-20. Saccharides of more than20 units are referred to herein as polysaccharides. The oligosaccharidesare poorly or non-digestible, i.e. are not readily converted to caloricsubstrates by the mammalian digestive enzymes.

The use of arabinose-containing polysaccharides in food products isknown. GB 1,072,029 discloses the use of arabinogalactans having amolecular weight in the range of 70-95 kDa (DP 450-600) as a bulksweetener combined with an artificial sweetener. According to U.S. Pat.No. 6,004,610, such arabinogalactans can be used together withhydrolysed guar gum as a dietary fibre in beverages, because of theirlow viscosity. WO 00/08948 (DE-198,36339) describes the use of acombination of an oligosaccharide (up to a hexasaccharide) and apolysaccharide (from a heptasaccharide upwards) for promoting flora ofthe human large intestine. Arabinans are mentioned as one of manypossible polysaccharides.

The oligosaccharides to be used according to the invention have at leastone terminal arabinose unit, i.e. at least one arabinose unit which islinked to the remainder of the oligosaccharide molecule by one(glycosidic) bond. These terminal arabinose units may be located at theend of the main chain of the oligosaccharide, whether it is a reducingend (having a free hemiacetal function) or a non-reducing end, or both,but they may also be located at the end of side chains to the main chainor be directly bound to the main chain by a single bond. In the presentdescription, the oligosaccharides having one or more terminal arabinoseunits are also referred to as “arabino-oligosaccharides”.

In its simplest form, an arabino-oligosaccharide of the invention is adimer of two saccharide residues substituted, at least one of which isan L-arabinose residue. The other saccharide residue may be chosen fromall saccharide residues, and in particular those saccharide residuesthat are present in naturally occurring saccharide polymers, such asgalactose, arabinose, mannose and xylose. Most preferably the othersaccharide is arabinose or galactose. Similarly, in trisaccharides, oneor both of the terminal saccharide units are arabinose residue, whilethe remaining ones can be galactose, xylose, mannose etc., and thecentral arabinose can also be arabinose.

Longer arabino-oligosaccharides may be straight-chain (unbranched) orpreferably branched oligosaccharides composed of any combination ofsaccharide units, as long as at least one terminal one is arabinose. Theoligosaccharides may be linked by α-links, at 1,2-, 1,3-, 1,4- and/or(if applicable) 1,5- or 1,6- positions and, if ketoses are involved,2,1-, 2,4-, 2,6- positions etc. L-Arabinose units in thearabino-oligosaccharides are usually in their furanoside form, but mayalso be in the pyranoside form. They are predominantly α-1,3- or α-1,5linked. The number of L-arabinose residues present in thearabino-oligosaccharides may vary, provided that at least one arabinoseresidue, preferably at least two arabinose units, are present on atleast one end of the oligosaccharide chain. Thus, only one (i.e. the atleast one terminal residue), several or essentially all of thesaccharide residues that form the backbone of the saccharide oligomermay be substituted with an L-arabinose residue. The backbone itself mayconsist of arabinose units or other units (galactoses, xyloses etc.).

The oligosaccharide units usually contain aldoses (and ketoses) only,but may also contain uronic acid, methylated or acylated or othercommonly derivatised units.

The arabino-oligosaccharide may be a pure, exactly definedoligosaccharide or, more commonly a mixture of oligosaccharides withvarying chain length and possibly also with varying branching patternsand/or varying saccharide composition. The arabino-oligosaccharides arepreferably of natural origin, either directly isolated from theirnatural source, or isolated and hydrolysed or synthesised by chainlengthening. Hydrolysis may be effected chemically (acid) orenzymatically (glycanases) as described below, and synthesis istypically effected enzymatically (transferases).

Some suitable sources of such naturally occurring insoluble polymersinclude sugar beet extract, which contains mainly linear arabinans,cereal fibre, e.g. of wheat and barley, which contains branchedarabino-xylo-saccharides (xylan chains which arabinose and other sideunits), and apple, potato and soybean fibre, which contain branchedarabinogalactans of various types. They may also originate fromarabinose-containing gums, such as gum arabic, tragacanth (the bassorinfraction thereof), gum ghatti etc.

The presence of one or more arabino-saccharides in a sample—such as thenutritional compositions of the invention and/or the hydrolysatesmentioned below—can be assayed using analytical techniques known per se,such as high performance anion-exchange chromatography (HPAEC), andtheir amounts can be determined e.g. by preparative gel filtrationfollowed by trifluoroacetic acid hydrolysis and HPAEC.

The nutritional composition of the invention may contain one or severaldifferent (types of) arabino-oligosaccharides. When the nutritionalcomposition of the invention contains several differentarabino-oligosaccharides, these may differ in their degree ofpolymerisation (DP, the total number of saccharide residues in theoligosaccharide chain); in the number and/or the position of theL-arabinose residues present on their oligosaccharide chain; in the(types of) the saccharide residues that form the oligosaccharide chain,the relative amounts thereof and/or the order thereof; and/or in anycombination thereof. Also, the arabino-oligosaccharides present in thenutritional composition of the invention may differ in the manner inwhich they were obtained and/or in the starting material from which theywere obtained, e.g. as further described below.

In the present invention, the arabino-oligosaccharides are preferablyprovided and incorporated into the nutritional composition in the formof a hydrolysate containing at least one arabino-oligosaccharide asdefined above. Such hydrolysates form a further aspect of the invention.Preferably, such hydrolysates are obtained by hydrolysis of a startingmaterial containing one or more L-arabinose-substituted polymers,preferably from natural origin. Of course, mixtures of such naturallyoccurring polymers and/or of such naturally available starting materialsmay also be used.

Generally, the hydrolysates of the invention will contain at least oneoligomer, and usually several different oligomers, depending upon thestarting material chosen, the way in which the starting material hasbeen hydrolysed, as well as the further processing, separation and/orpurification steps applied after hydrolysis (if any).

Furthermore, besides the desired arabinose-terminated oligomers, thehydrolysates of the invention may also contain amounts of arabinosemonomers and other saccharide monomers. They may also contain amounts ofarabinose-substituted saccharide polymers with a degree ofpolymerisation (chain length) of more than 20. Again, this will dependupon the starting material chosen, the way in which the startingmaterial has been hydrolysed, as well as the further processing,separation and/or purification steps applied after the hydrolysis, ifany.

According to the invention, it has been found that, in the nutritionalcompositions of the invention, the presence of certain amounts ofmonomers of polymers (including insoluble polymers) will not essentiallyinfluence (e.g. detract from) the health promoting action of theL-arabinose substituted oligomers of the invention, and also otherwisecan be tolerated. However, preferably, the amount of oligomers in thehydrolysates used in the nutritional compositions of the invention is atleast 5%, preferably at least 20%, based upon the total amount ofoligomers, monomers and polymers (including insoluble polymers) presentin the hydrolysates.

Thus, the hydrolysates that are incorporated into the nutritionalcompositions of the invention may contain, as far asarabinose-containing carbohydrates are concerned (weight ratios): 0-50%of monomers, 10-100% of oligomers (2- to 20-mers) and 0-70% of polymers(>20-mers). Preferably the ratios are 2-40% of monomers, 20-80% ofarabinose-containing oligomers, 2-40% of other oligomers, and 10-60% ofpolymers. Most preferably, the ratios are 35-75% of arabinose-containingoligomers, 5-30% of other non-digestible oligomers, 5-30% of monomers,and 15-35% of non-digestible polymers.

The hydrolysis of the starting polymers—i.e. to provide the abovehydrolysates—may be carried out in any manner known per se, dependingupon the starting material used and the desired hydrolysate. Acidhydrolysis and enzymatic hydrolysis are preferred, with enzymatichydrolysis being particularly preferred. Suitable conditions for acidhydrolysis include the use of aqueous media containing acids such ashydrochloric acid, sulphuric acid, phosphoric acid, an organic acid orpolymeric or immobilised acids (acid resin) under usual conditions.

For enzymatic hydrolysis, any enzyme or enzyme combination suitable fordegrading the starting polymers may be used. Preferably, these areendo-enzymes, and suitable examples and sources thereof will be clear tothe skilled person. Enzymatic synthesis can be performed withtransferase, i.e. enzymes capable of transferring an arabinose residueto a mono- or oligosaccharide.

Suitable conditions for enzymatic hydrolysis will depend upon thestarting material and the enzyme used. Preferably, a pH and atemperature near the optimum pH and temperature of the enzyme is used.Suitable conditions may for instance comprise the use of purifiedendogalactanase of 1 μg/ml in an aqueous substrate solution at a pHbetween 4.5 and 6, at a temperature of about 30° C. for 30 minutes to 3hours at a concentration of starting arabinogalactan of 0.5-20 wt. %. Aswill be clear to the skilled person, the starting materials, the enzymesused, the hydrolysis conditions and the optional further processingsteps most preferably are chosen such that the resulting hydrolysate isstill acceptable for use in the nutritional compositions of theinvention. Usually, this will involve the use of starting materials,enzymes etc. acceptable for use in food applications, e.g. having theGRAS status.

Generally, the hydrolysis is allowed to proceed until the hydrolysateobtained contains at least 10%, preferably at least 20%, most preferablyat least 50% arabinose-containing oligomers. The progress of thehydrolysis may be followed using any suitable method, which will usuallyinvolve determining the amount of the oligomers formed, the amount ofmonomers formed, and/or the amount of polymers remaining. Suitabletechniques, such as chromatography techniques, will be clear to theskilled person. The arabinose-containing starting polymers may be usedas such, or may be purified so as to increase the yield of desiredproduct. Such pre-treatment may include chemical extraction (sodiumhydroxide solution) or physical extraction (extrusion).

For instance, for the degradation of naturally occurring polymersmentioned below, and for the transfer synthesis, respectively, thefollowing enzymes be used:

Starting material Enzyme Oligomer arabinan endo-arabinasearabino-oligosaccharides arabinoxylan endo-xylanase arabinoxylo-oligosaccharides arabinogalactan endo-galactanase arabinogalacto-oligosaccharides arabinobiose arabinofuranohydrolase arabinotriose andhigher homologues

The hydrolysates obtained after the hydrolysis may be incorporated assuch into the nutritional compositions of the invention, or afterfurther processing/purification steps, for instance to quench thehydrolysis reaction (e.g. to inactivate the enzyme(s) and/or to increasethe pH), to remove components of the hydrolysis mixture such as saltsand/or the enzymes used; to remove byproducts of the hydrolysisreaction; and/or the reduce the amount of monomers or the amount ofsoluble or insoluble polymers. This may be carried out using anypurification and/or processing techniques known per se, includingneutralisation, precipitation, filtration, dialysis, ultrafiltration, ora suitable combination of such steps. These steps preferably result in ahydrolysate as described above for incorporation in the nutritionalcompositions of the invention.

Also, a nutritional composition of the invention may contain acombination of such hydrolysates, i.e. obtained from different startingmaterials, using different hydrolysis conditions (e.g. enzymes usedand/or final degree of hydrolysis) and/or different furtherpurification/processing steps.

Thus, in a further aspect, the invention relates to a method forpreparing a hydrolysate containing at least one L-arabinose substitutedoligosaccharide, said method comprising hydrolysing one or moreL-arabinose substituted polymers and optionally one or more furtherprocessing steps known per se.

The invention is based on the discovery that the oligomeric arabans havea health-promoting action, in particular with respect to the preventionand/or treatment of disorders of the gastrointestinal tract. Inparticular, it has been found that the arabino-oligosaccharides canprevent and/or reduce adhesion or translocation of undesiredmicro-organisms to the intestinal wall, and also have a “bifidogenic”effect, by which is meant that they can promote a healthy flora in thegastrointestinal tract, which in infants makes it more similar to theflora of breast-fed infants and/or can be used to prevent and/or treatany disturbance in the naturally occurring flora in the gastrointestinaltract. These effects are especially beneficial in clinical patients andin newborns. Also, the products induce an enhanced immune function andan improved absorption of minerals like calcium and magnesium, which isbeneficial to menopausal woman, elderly persons, and patients sufferingfrom a disturbed intestinal function.

The compositions of the invention may provide their health-promotingaction throughout the entire small and large intestine and/or one ormore parts thereof, including the duodenum, jejunum, ileum and colon.Similarly, the compositions of the invention may also provide theiranti-adhesion and/or their bifidogenic effect throughout the entireintestinal tract and/or parts thereof, which may be the same ordifferent parts.

For this purpose, the nutritional compositions of the invention maycontain several different oligomers, which may provide for healthpromoting action in different parts of the gastrointestinal tract. Also,the nutritional compositions of the invention may contain severaldifferent oligomers, one or more of which provide for an anti-adhesioneffect and one or more of which provide for a bifidogenic effect. Also,nutritional compositions of the invention may contain differentoligomers (e.g. with different degrees of hydrolysis) so as to providefor an anti-adhesion effect in different parts of the gastrointestinaltract, and/or several different oligomers (e.g. with different degreesof hydrolysis) as to provide for a bifidogenic effect in different partsof the gastrointestinal tract.

In this way, oral administration of a nutritional composition of theinvention containing several different oligomers, suitably chosen, canproduce the desired health-promoting action in several or in essentiallyall parts of the gastrointestinal tract simultaneously. Also, by oraladministration of such a composition, both an anti-adhesion and abifidogenic effect can be obtained simultaneously, in one, several oressentially all parts of the gastrointestinal tract, which may be thesame of different. Also, by using a combination of several differentoligomers, a synergistic effect may be obtained.

According to one preferred aspect, the nutritional compositions of theinvention provide their anti-adhesion effect in the small intestineand/or provide their bifidogenic effect in the large intestine.Generally, for an anti-adhesion effect, small linear and branchedoligomers, preferably with a degree of polymerisation (DP) of 2-10 aremost suited. For a bifidogenic effect, oligomers which are branched andhave a DP of up to 20 are most suited.

Generally, to obtain the health promoting action effect of theinvention, the oligomers will usually be administered to an adult in anamount ranging between 0.01 and 0.5 g per kg body weight per day; and toan infant in an amount ranging between 0.02 and 1.0 g per kg body weightper day. These amounts of oligomers may be administered as a single doseper day or as several doses per day, with 1-6, in particular 1-3 dosesper day being preferred.

More specifically, to obtain the anti-adhesion effect of the invention,the arabino-oligosaccharides will usually be administered to an adult inan amount ranging from 0.01 to 0.2 g per kg body weight per day; and toan infant in an amount ranging from 0.02 to 0.4 g per kg body weight perday; again as a single or as several doses per day.

To obtain the bifidogenic effect of the invention, the oligomers willusually be administered to an adult in an amount between 0.1 and 0.5 gper kg body weight per day; and to an infant in an amount between 0.2and 1.0 g per kg body weight per day; also as a single or as severaldoses per day.

From the above, it will be clear that—as the amount ofarabino-oligosaccharides that is usually administered to obtain thebifidogenic effect is larger than the amount usually administered toobtain the anti-adhesion effect—administering thearabino-oligosaccharides to obtain the bifidogenic effect will usuallyalso result in a anti-adhesion effect, depending upon the oligomerspresent.

The administration of the nutritional compositions of the invention maybe continued until the desired health promoting action is obtainedand/or—when administered as prophylactics—until the individual is nolonger exposed to conditions which require (additional) protectionagainst disorders of the gastrointestinal tract.

The nutritional composition of the invention may be in any form suitablefor human administration, and in particular suitable for administrationto any part of the gastrointestinal tract. Usually, and preferably, thiswill involve (compositions suitable for) oral administration, althoughfor instance administration into the gut—such as through a tube orcatheter—also forms part of the invention.

In particular, the nutritional composition may be in the form of a foodsupplement or in the form of a complete food which is ready forconsumption, such as a total food or infant formula.

When the composition of the invention is in the form of a foodsupplement, it can be in a form for separate administration, such as acapsule, a tablet, a powder, a sachet, a liquid composition (e.g.droplets) or a similar form, containing preferably a unit dose ofoligomers of the invention. Such a supplement may further comprise oneor more adjuvants, carriers or excipients suitable for use in foodsupplements, as well as one or more of the further components and/oradditives described below.

The food supplement may also be in the form of a powder, a liquidcomposition (e.g. droplets) or a similar form, which is added to ormixed with a suitable food (composition) or a suitable liquid or solidcarrier, for the preparation of a food or drink which is ready forconsumption. For instance, the food supplement may be in the form of apowder which can be mixed with, and/or reconstituted with, water, milk,fruit juice, toddler drinks, oral rehydration solution (to provide aso-called ORS drink), etc. It can also be in the form of a powder orliquid that can be mixed with solid foods or with foods with ahigh-water-content, such as fermented foods, for example yoghurt.

A food supplement according to the invention preferably contains thenon-digestible arabinose-containing oligosaccharides (1) together withnon-digestible polysaccharides (3) (whether or not containing arabinoseunits), optionally other non-digestible oligosaccharides (2) anddigestible carbohydrates (4), such as glucose, fructose, and/ormalto-dextrins, in a weight ratio of (1)+(2)+(3) to (4) of 1:5 to 24:1.The amount of (1) is 1-90% of the total dry weight of the supplement,preferably 5-40%, the amount of (2) is 0-50%, preferably 2-25%, theamount of (3) is 2-50%, preferably 5-30%, and the amount of (4) is4-80%, preferably 10-50%. The remainder, if any, may be vitamins,minerals, proteins, colorants, preservatives and the like.

The nutritional compositions of the invention can also be in the form ofa solid, semi-solid or liquid food which is ready for consumption. Sucha food will usually comprise—besides the one or more oligomers of theinvention—a food or food base known per se, and can for instance beprepared by

-   -   adding a food supplement as described above to a food or food        base known per se;    -   adding one or more oligomers of the invention to a food or food        base known per se; and/or    -   incorporating one or more oligomers of the invention to a food        or food base known per se during the preparation thereof.

As such, the nutritional compositions in the invention can be foods fororal consumption, for instance a total food or an infant formula. Theycan also be foods for administration by tube or catheter into thestomach, e.g. by tube or catheter.

The nutritional composition of the invention, whether in the form of afood for consumption or a food supplement, can further comprise alldesired components and/or additives for use in foods or foodsupplements, including but not limited to flavours, colourings,preservatives, sugar, etc., as long as these do not interfere (too much)with the desired health promoting action of the oligomers. Thecomposition can contain one or more peptides and/or proteins, lipids,carbohydrates, vitamins, minerals and trace elements, in usual amounts.

A complete food according to the invention preferably comprises proteins(4-35%, preferably 7-25%), lipids (4-40%, preferably 7-35%), digestiblecarbohydrates (30-90%, preferably 35-75%), in addition to 0.07-6%,preferably 0.2-4% of non-digestible arabinose-containingoligosaccharides. The balance up to 100% (all percentages by weight) maybe other non-digestible carbohydrates, e.g. in a proportion of 0-10%,preferably 0.1-5%, at least half of which preferentially consists ofoligosaccharides. Where the complete food is a tube-feeding, the amountof non-digestible arabinose-containing oligosaccharides is preferably0.07-2.5%, in particular 0.2-2%. In an infant formula, the amount ofnon-digestible arabinose-containing oligosaccharides is preferablyhigher, i.e. 0.15-6%, in particular 0.4-4%.

The composition of the invention can also contain one or more additionalsubstances that inhibit bacterial adhesion to the epithelial wall of thegastrointestinal tract, including mannans, galacturonic acid oligomers,preferably of natural origin, as a result of which a synergistic effectmay be obtained.

The compositions can and preferably do also contain prebiotics, as wellas prebiotic compounds, in particular fibres and proteins. Fibres inparticular include soluble and insoluble non-digestible polysaccharides,such as non-starch polysaccharides (of the cellulose, hemicellulose andother types), resistant starch, gums etc. It is particularly preferredthat the compositions of the invention comprise other non-digestibleoligosaccharides, which are usually soluble. These include(trans-)galacto-oligosaccharides (TOS or GOS), fructo-oligosaccharides(FOS), xylo-oligosaccharides (XOS) and manno-oligosaccharides. Theseother oligosaccharides are preferably obtained from natural sources,either by direct extraction, e.g. in the case of inulin (FOS), or byhydrolysis of suitable polysaccharide or polysaccharide mixture, e.g. inthe case of inulin and levan (FOS), galactans and galactomannans (TOS),and xylans and other hemicellulose constituents (XOS) or by enzymaticsynthesis using the appropriate transferases, e.g. in the case of FOSand TOS.

These other oligosaccharides may be added as such, especially if theyare obtained by direct extraction or synthesis (FOS or TOS) or they maybe co-hydrolysed with the arabino-polysaccharides to obtain anoligosaccharide fraction containing both arabino-oligosaccharides of theinvention and other oligosaccharides, e.g. xylo- and/orgalacto-oligosaccharides. These may (further) help to maintain and/orrestore the intestinal flora, which again may result in a synergisticeffect. The amounts of other oligosaccharides may vary, e.g. from 10% to400% with respect to the total amount of non-digestibleoligosaccharides, especially in a ratio of arabino-oligosaccharides(AOS) to other oligosaccharides between 1:3 and 3:1.

The compositions may advantageously also contain probiotic organismssuch as bifidobacteria, lactobacilli and other lactic acid bacteria,e.g. at levels of at least 10⁷ viable micro-organisms per daily dose perindividual.

The compositions of the invention may also contain antibodies such asimmuno-globulins that act specifically against the pathogenicmicro-organisms, more specifically against enterotoxigenic E. coilstrains, rotaviusses, Clostridia, Salmonella and/or Campylobacterspecies. These immunoglobulins are used in amounts of at least 20 μg per100 g of the composition. The compositions can also contain at least 2mg/100 g of the composition sialylated compounds, and at least 2 mg/100g product of a bactericidal compound, such as preferably lactoferrin.

Also, the compositions of the invention may contain otherhealth-promoting components known per se, such as medicaments, etc. Inparticular, the compositions may contain compounds which have abeneficial influence on the gastro-intestinal tract, such asglutamine/glutamate or precursors thereof, which provide fuel for thecells of the gastrointestinal wall. Again, by the use of such acombination, a synergistic effect may be obtained.

The amount of the one or more oligomers described above that is presentin a nutritional composition of the invention will usually dependupon—inter alia—the oligomers used, the form of the composition (e.g. asa total food or as a food supplement), the intended health promotingeffect (e.g. adhesion inhibiting and/or bifidogenic), and the number ofdoses per day to be administered. Generally, the amount will be suchthat it allows easy administration of the oligomers in the daily amountsmentioned above, e.g. as a single dose or as several doses per day.

Amounts to be administered are given below with reference to a dailydosage, unless indicated otherwise. A daily dosage for an adult is takenas corresponding to an energy intake of 2000 kcal/day, or about 25 kcalper kg body weight per day. Thus, an amount given as a daily dosage,where complete foods are concerned, means an amount per 2000 kcal energyfor an adult. For an infant, the energy intake is usually higher e.g.about 50 kcal per kg body weight per day. For food supplements, theamount are naturally higher: if the supplement contains energycomponents, such as carbohydrates, the amount per daily dosage may bee.g. the amount per 200 or per 400 kcal energy. The amounts given mayalso refer to the total weight of the nutritional composition as givenbelow and in the appending claims.

Usually, a nutritional composition of the invention will contain a unitdose of the oligomers and/or a predetermined amount of hydrolysate. Forinstance, a food supplement of the invention may contain a total of 0.3to 10.0 g of arabinose-containing oligomers, and/or a total of 2.5 to 50g of hydrolysate of the invention. Preferred amounts are between 0.5 and8 g oligomers and between 5 and 25 g hydrolysate. A total food of theinvention may for instance contain a total of 0.5 to 10.0 g of oligomers(preferred 1.0 to 8 g), and/or a total of 2.5 to 50 g (preferred 5 to 25g) of hydrolysate of the invention. A infant formula of the inventionmay for instance contain a total of 0.5 to 10.0 g (preferred 1.0 to 8.0g) of oligomers, and/or a total of 1 to 20 g (preferred 2.0 to 16.0 g)of the hydrolysate of the invention.

The nutritional compositions of the invention can be used to prevent ortreat any of a number of disorders of the gastrointestinal tract, and/orreduce or alleviate the symptoms of such disorders. These disordersinclude, but not limited to infectious diarrhoea, traveller's diarrhoea,antibiotic-associated diarrhoea. The compositions of the invention areparticularly suited for the prevention of infectious diarrhoea caused bymicro-organisms such as E. coli or Shigella, as may occur during traveland/or after treatment with antibiotics.

For these and other applications, the oligomers provide the followingeffects and advantages:

-   -   they reduce and/or prevent of the adhesion of pathogens such        as E. coli (HEC) and Shigella to the (wall of) the        gastrointestinal tract, and in particular the intestinal wall;        this reduces the risk of infection;    -   they promote the natural flora in the gastrointestinal tract and        thereby reduce or prevent the growth of pathogens;    -   they promote and/or restore normal digestion and a proper        electrolyte balance in the gastrointestinal tract.

In these and other applications, some further advantages of the use ofthe oligomers include:

-   -   they stimulate growth of species of bifidobacteria which are not        stimulated by e.g. TOS, which is also considered as a prebiotic;    -   the fermentation of the oligomers of the invention may improve        the absorption from calcium from the colon;    -   the oligomers have a viscosity which makes them particularly        suited for the preparation of food for administration into the        stomach by tube or catheter.

In a further aspect, the invention therefore relates to the use of atleast one oligomer, and/or of an hydrolysate containing at least oneoligomer as described above, in (the preparation of) a nutritionalcomposition for the prevention and/or treatment of disorders of thegastrointestinal tract, such as disorders listed above, in particularfor the prevention and/or treatment of diarrhoea, and in particularinfectious diarrhoea.

The invention also relates to the use of at least one oligomer, and/orof an hydrolysate containing at least one oligomer as described above,in (the preparation of) a nutritional composition for reducing and/orpreventing the adhesion and/or the growth of undesired micro-organismssuch as pathogens to the (wall of) the gastrointestinal tract.

Also, in a further aspect, the invention also relates to the use of atleast one oligomer, and/or of an hydrolysate containing at least oneoligomer as described above, in (the preparation of) a nutritionalcomposition for promoting or restoring the natural intestinal flora,and/or for preventing or reducing a disturbance of the naturalintestinal flora.

Although the oligomers of the invention most preferably have a degree ofpolymerisation of 2-20, it should be clear that some health-promotingaction may also be provided by oligomers of the general type, but with asomewhat larger degree of polymerisation, e.g. in the region of 21-30.Thus, although not preferred, the use of minor amounts of sucholigomers, if it results in a health promoting action as describedherein, should be considered equivalent to the embodiments describedabove.

EXAMPLES Example 1 Production of Arabiizo-oligosacchiarides

Commercial sugar beet fibre (Atlantis series 2025) containing 80%dietary fibre, about half of which is soluble, contains about 39%arabinose (determined using HPAEC after TFA hydrolysis). The fibre isdissolved in acetate buffer (50 mM, pH 5) and is incubated at 40° C.with an endo-arabinase, e.g as present in commercial enzyme preparationUltra SP (Novo Nordisk). After the incubation period, the reaction isstopped using a heating step (100° C.). The product is spray-dried andcontains about 10% of monomer (largely arabinose), 20% ofarabino-oligosaccharides (DP 2-6), 10% other oligosaccharides (DP 2-20),10% soluble fibre (DP >20) and 50% insoluble fibre (DP>20).

Example 2 Production of Arabino-oligosaccharides

Arabinan (Megazyme, 50% arabinose in polymer form) was incubated withUltra SP (10 μl) for 3 h at 40° C. and pH 5. After deactivation of theenzyme, the product was freeze-dried and analysed using HPAEC. After 3 hof incubation, the carbohydrate fraction consisted of about 25% ofmonomer, 40% of arabino-oligosaccharides (DP 2-20), 10% otheroligosaccharides (containing no arabinoses) and 25% of material having aDP above 20. After filtration over a 0.1 mm filter, the sterile liquidis spray-dried.

Example 3 Anti-adhesive Effect

Different oligosaccharides obtained by hydrolysis of fibres were used tomeasure inhibition of pathogen binding to human colon cancer cells.Cells for the binding experiment are grown under standard conditions.The growth medium is removed from the cells and 0.2 ml of minimalessential medium, 0.4 ml EHEC solution (2×10⁸ cfu/ml) and 0.4 ml of testsolution (5-10 mg/ml hydrolysed fibre) is added. Appropriate blanks areused as controls. Cells are incubated for an hour at 37° C., after whichthe medium is removed. The cells are washed five times with PBS buffer,lysed, homogenised, diluted and plated to count colony-forming units,following standard procedures. Comparison of the amount of cfu's foundwith the blank and with one of the fractions, the inhibiting power ofthe fraction can be calculated as percentage reduction in binding. Thetable below summarises results of binding reduction. The results showthat arabinose-containing oligosaccharides reduce the binding of EHEC toCaco2 cells better than any of the other oligosaccharides. Especiallyarabino-oligosaccharides shows very high binding reduction capacity butalso arabinoxylo- and arabinogalacto-oligosaccharides show more that 60%reduction in binding. All other oligosaccharides (nonarabinose-containing) have lower than 60% binding reduction activity.

oligosaccharide % binding reduction arabinan 91 arabinoxylan 75arabinogalactan 63 galactan 52 xylan  3 galactomannan 24 galacturonan 21lactose 28

Example 4 Bifidogenic Effect

Hydrolysed arabans (DP 2-9, containing about 10% monomer) from sugarbeet (see example 3) stimulate the growth of Bifidobacterium strains:lactis, infantis, angulatum and pseudocatelulatum.

When 150 mg of specific oligosaccharides is added to 5 g faeces, thegrowth of bifidobacteria increases. When the oligosaccharides aretrans-galacto-oligosaccharides, the bifidobacteria content increaseswith 5%. When the oligosaccharides are arabino-galactans, the numberincreases by about 38% toe over the same time period. When arabinoseoligomers are used, the increase is about 68%.

Example 5 Nutritional Composition

An infant formula is prepared by mixing the following components.

Component g per 100 ml Protein equivalents 1.40 Casein 0.60 Whey protein0.80 Carbohydrates 7.0 Lactose 1.3 Glucose 0.2 Maltose 2.1Polysaccharides 3.5 Lipids 3.6 Saturated 1.4 Mono-unsaturated 1.7Poly-unsaturated 0.5 Arabino-oligosaccharides according to example 1 0.1Further components: minerals, trace elements and vitamins in amounts asrecommended by the EEC regulation 321.

Example 6 Supplement for the Treatment of Diarrhoea

The product of example 2 (10 kg dry weight), glucose (20 kg), potassiumcitrate (2.9 kg) and sodium chloride (3.2 kg) are dissolved in water toa total of 1000 1 in a tank to produce a liquid.

Example 7 Supplement for Enhancing Intestinal Function

A mixture of 2 g of hydrolysed arabinoxylans, 2 g offructo-oligosaccharides, 2 g of soy polysaccharides, 1 g of a probioticpreparation containing about 10¹⁰ freeze-dried lacto-bacillus cells, 5 gmaltodextrs and flavourings is prepared as a daily dosage form of 12 gpackaged in sachets. It improves the intestinal function.

1. A complete food composition containing proteins (4-35wt. %), lipids(4-35 wt. %), and digestible carbohydrates (30-90 wt. %), saidcomposition containing, on a dry weight basis, 0.07-6% ofarabinoxylo-oligosaccharides containing at least one L-arabinose unit atleast one end of the oligosaccharide chain.
 2. A complete foodcomposition according to claim 1, which is a liquid tube-feedcomposition containing, on a dry weight basis, 0.07-2.5% of saidarabinose-containing oligosaccharides.
 3. A complete food compositionaccording to claim 1, which is an infant formula containing, on a dryweight basis, 0.15-6% of said arabinose-containing oligosaccharides.